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Microbiome profiling reveals gut dysbiosis in a transgenic mouse model of Huntington's disease
Open accessAbstract
Huntington's disease (HD) is a progressive neurodegenerative disorder caused by a trinucleotide repeat expansion in the huntingtin (HTT) gene, which is expressed ubiquitously throughout the brain and peripheral tissues. Whilst the focus of much research has been on the cognitive, psychiatric and motor symptoms of HD, the extent of peripheral pathology and its potential impact on central symptoms has been less intensely explored. Disruption of the gastrointestinal microbiome (gut dysbiosis) has been recently reported in a number of neurological and psychiatric disorders, and therefore we hypothesized that it might also occur in HD. We have used 16S rRNA amplicon sequencing to characterize the gut microbiome in the R6/1 transgenic mouse model of HD, relative to littermate wild-type controls. We report that there is a significant difference in microbiota composition in HD mice at 12 weeks of age. Specifically, we observed an increase in Bacteriodetes and a proportional decrease in Firmicutes in the HD gut microbiome. In addition, we observed an increase in microbial diversity in male HD mice, compared to wild-type controls, but no differences in diversity were observed in female HD mice. The gut dysbiosis observed coincided with impairment in body weight gain despite higher food intake as well as motor deficits at 12 weeks of age. Gut dysbiosis was also associated with a change in the gut microenvironment, as we observed higher fecal water content in HD mice at 12 weeks of age. This study provides the first evidence of gut dysbiosis in HD.
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“Moreover, a higher relative abundance of Bacteroidetes and a lower relative abundance of Firmicutes were reported in both R6/1 and R6/2 mice, as compared to WT mice.235,236”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [235]
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“However, the study did not observe an increase in Bacteroidetes and a reduction in Firmicutes, as reported in both R6/1 and R6/2 mice.235,236”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [235]
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“A notable difference in gut microbiota composition was observed between R6/1 mice and wild-type (WT) mice at 12 weeks of age (early disease stage), which coincided with the manifestation of motor deficits and weight loss.235”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [235]
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Metadata
- Authors
- Kong, G., Cao, K.-A. L., Judd, L. M., Li, S., Renoir, T., & Hannan, A. J.
- Affiliations
- The University of Melbourne (AU)
- Corresponding author
- Hannan, Anthony J.
- Venue
- Neurobiology of Disease
- Publisher
- Elsevier BV
- Published
- 2020-02
- Volume
- 135
- Pages
- 104268
- ISSN
- 0969-9961 (ISSN-L)
- OpenAlex
- W2889638535
- Cited by
- 212
- References
- 60
- Citations by year
- 2026: 13 · 2025: 35 · 2024: 39 · 2023: 27 · 2022: 37 · 2021: 32 · 2020: 20
- FWCI
- 5.34
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Neurobiology of Disease (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- NHMRC (GNT1087415)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Genetic Neurodegenerative Diseases
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Keywords
- Huntington's disease, gut dysbiosis, gut microbiota, Bacteroidetes, Firmicutes, microbial diversity, sex differences, weight gain, motor impairment, fecal water content
- MeSH terms
- Gastrointestinal Microbiome, Huntingtin Protein, Animals, Brain, Disease Models, Animal, Huntington Disease, Male, Mice, Transgenic, Motor Activity, Nerve Tissue Proteins, Trinucleotide Repeat Expansion, Dysbiosis
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